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GRB2-associated and regulator of MAPK protein (GRB2-associated and regulator of MAPK1)

 GARE1_MOUSE             Reviewed;         876 AA.
Q3UFT3; G5E8B7; Q3TSA2; Q5DTF6; Q80V96;
06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
03-OCT-2012, sequence version 2.
05-JUN-2019, entry version 101.
RecName: Full=GRB2-associated and regulator of MAPK protein;
AltName: Full=GRB2-associated and regulator of MAPK1;
Name=Garem1; Synonyms=Fam59a, Garem, Gm944, Kiaa4238;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=C57BL/6J;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Brain;
Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
Koga H.;
"Prediction of the coding sequences of mouse homologues of KIAA gene.
The complete nucleotide sequences of mouse KIAA-homologous cDNAs
identified by screening of terminal sequences of cDNA clones randomly
sampled from size-fractionated libraries.";
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=C57BL/6J;
PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
Lindblad-Toh K., Eichler E.E., Ponting C.P.;
"Lineage-specific biology revealed by a finished genome assembly of
the mouse.";
PLoS Biol. 7:E1000112-E1000112(2009).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 219-876 (ISOFORM 1).
TISSUE=Mammary gland;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-609 AND SER-613, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Spleen;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
-!- FUNCTION: Acts as an adapter protein that plays a role in
intracellular signaling cascades triggered either by the cell
surface activated epidermal growth factor receptor and/or
cytoplasmic protein tyrosine kinases. Promotes activation of the
MAPK/ERK signaling pathway. Plays a role in the regulation of cell
proliferation (By similarity). {ECO:0000250}.
-!- SUBUNIT: Interacts with EGFR. Interacts (via proline-rich domain
and phosphorylated at Tyr-105 and Tyr-453) with GRB2 (via SH3
domains); the interaction occurs upon EGF stimulation. Interacts
(phosphorylated at Tyr-453) with PTPN11; the interaction increases
MAPK/ERK activity and does not affect the GRB2/SOS complex
formation (By similarity). {ECO:0000250}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q3UFT3-1; Sequence=Displayed;
Name=2;
IsoId=Q3UFT3-2; Sequence=VSP_023049, VSP_023050;
-!- PTM: On EGF stimulation, phosphorylated on Tyr-105 and Tyr-453.
{ECO:0000250}.
-!- SIMILARITY: Belongs to the GAREM family. {ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=BAD90542.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
-----------------------------------------------------------------------
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EMBL; AK148318; BAE28477.1; -; mRNA.
EMBL; AK162177; BAE36773.1; -; mRNA.
EMBL; AK220564; BAD90542.1; ALT_INIT; mRNA.
EMBL; AC127570; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AC158774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH466557; EDK96964.1; -; Genomic_DNA.
EMBL; BC049983; AAH49983.1; -; mRNA.
CCDS; CCDS29091.1; -. [Q3UFT3-1]
RefSeq; NP_001028617.2; NM_001033445.2. [Q3UFT3-1]
SMR; Q3UFT3; -.
IntAct; Q3UFT3; 1.
STRING; 10090.ENSMUSP00000048914; -.
iPTMnet; Q3UFT3; -.
PhosphoSitePlus; Q3UFT3; -.
MaxQB; Q3UFT3; -.
PaxDb; Q3UFT3; -.
PRIDE; Q3UFT3; -.
Ensembl; ENSMUST00000049260; ENSMUSP00000048914; ENSMUSG00000042680. [Q3UFT3-1]
Ensembl; ENSMUST00000234115; ENSMUSP00000157254; ENSMUSG00000042680. [Q3UFT3-2]
GeneID; 381126; -.
KEGG; mmu:381126; -.
UCSC; uc008efg.1; mouse. [Q3UFT3-1]
UCSC; uc008efh.1; mouse. [Q3UFT3-2]
CTD; 64762; -.
MGI; MGI:2685790; Garem1.
eggNOG; ENOG410II0U; Eukaryota.
eggNOG; ENOG410XSPW; LUCA.
GeneTree; ENSGT00530000063834; -.
HOGENOM; HOG000074085; -.
InParanoid; Q3UFT3; -.
OMA; GGEWAPF; -.
OrthoDB; 288834at2759; -.
TreeFam; TF329726; -.
ChiTaRS; Garem; mouse.
PRO; PR:Q3UFT3; -.
Proteomes; UP000000589; Chromosome 18.
Bgee; ENSMUSG00000042680; Expressed in 246 organ(s), highest expression level in caudate-putamen.
Genevisible; Q3UFT3; MM.
GO; GO:0070064; F:proline-rich region binding; ISS:UniProtKB.
GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISS:UniProtKB.
GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
Gene3D; 1.10.150.50; -; 1.
InterPro; IPR025946; CABIT_dom.
InterPro; IPR013761; SAM/pointed_sf.
Pfam; PF12736; CABIT; 1.
SUPFAM; SSF47769; SSF47769; 1.
1: Evidence at protein level;
Alternative splicing; Complete proteome; Mitogen; Phosphoprotein;
Reference proteome.
CHAIN 1 876 GRB2-associated and regulator of MAPK
protein.
/FTId=PRO_0000277648.
DOMAIN 811 876 SAM.
REGION 12 320 CABIT.
REGION 498 550 Necessary for interaction with GRB2.
{ECO:0000250}.
COMPBIAS 491 566 Pro-rich.
MOD_RES 105 105 Phosphotyrosine.
{ECO:0000250|UniProtKB:Q9H706}.
MOD_RES 453 453 Phosphotyrosine.
{ECO:0000250|UniProtKB:Q9H706}.
MOD_RES 609 609 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 613 613 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
VAR_SEQ 578 578 I -> M (in isoform 2).
{ECO:0000303|Ref.2}.
/FTId=VSP_023049.
VAR_SEQ 579 876 Missing (in isoform 2).
{ECO:0000303|Ref.2}.
/FTId=VSP_023050.
CONFLICT 324 324 H -> N (in Ref. 1; BAE28477).
{ECO:0000305}.
CONFLICT 652 652 P -> H (in Ref. 1; BAE28477).
{ECO:0000305}.
CONFLICT 857 857 L -> Q (in Ref. 1; BAE36773).
{ECO:0000305}.
SEQUENCE 876 AA; 97250 MW; 8CC941A2A072DE0A CRC64;
MDPAPSLGCS LKDVKWSPVA MPLDLLVSTY RLPQIARLDS GECVEGLREN DFLLIHSCRQ
WTTITAHSLE EGHYVIGPKI EIPVHYAGQF KLLEQDRDIK EPVQYFNSVE EVAKAFPERV
YVMEEITFNV KVASGECNED TEVYNITLCT GDELTLMGQA EILYAKTFKE KSRLNTIFKK
IGKLNSISKL GKGKMPCLIC MNHRTNESIS LPFQCKGRFS TRSPLELQMQ EGEHTIRNIV
EKTRLPVNVT VPSPPPRNPY DLHFIREGHR YKFVNIQTKT VVVCCVLRNN KILPMHFPLH
LTVPKFSLPE HQVKGDMWPE TLVHHWLGIC QEQFDIDEYS RAVRDVKTDW NEDCKSPKKG
RCSGHNHLPN SLSYARDELT QSFHRLSVCV YGNNLHGNSE VNLHGCRDLG GEWAPFPHDI
LPYQDSGDSG SDYLFPEANE ESAGIPGKTE VPYEELWLEE GKPSRQPLTR SLSEKSRCDT
LRGSTRSTCA PSSPPTPATL GATIKSSEIA LPPPPVPPKS EAVREECRLL NAPPVPPRSA
KPLSTSPSIP PRTVKPVRPQ TRSPSPTLSY YSSGLHNIIT QSDTSPPNSA PVSCYPCTRV
KSDSVDPKSP FGSPSAEALS SRLSWPNHYS GASENQTRSD FLLDPSRSYS YPRQKTPGTP
KRTCPAPFDF EGCELLGSPP STTSAEFSSS GVPSCPKSAS YCLENSEDNS FAAGMTKQSV
SCPALPPRAP KPVEQKATPE TSPLPLKIDG AEEDPTAGSL DLSEDQYFVR KGMQDIFSVS
YPFSSPLHLQ LAPRSCGDGS PWQPPADLSG LSIEEVSKSL RFIGLSEDVI AFFVTEKIDG
NLLVQLTEEI LSEDFKLSKL QVKKILQFIN GWRPKI


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Related Genes :
[GAREM1 C18orf11 FAM59A GAREM] GRB2-associated and regulator of MAPK protein 1 (GRB2-associated and regulator of MAPK1)
[GRB2 ASH] Growth factor receptor-bound protein 2 (Adapter protein GRB2) (Protein Ash) (SH2/SH3 adapter GRB2)
[Grb2] Growth factor receptor-bound protein 2 (Adapter protein GRB2) (SH2/SH3 adapter GRB2)
[Garem1 Fam59a Garem Gm944 Kiaa4238] GRB2-associated and regulator of MAPK protein (GRB2-associated and regulator of MAPK1)
[Grb2 Ash] Growth factor receptor-bound protein 2 (Adapter protein GRB2) (Protein Ash) (SH2/SH3 adapter GRB2)
[GRB2] Growth factor receptor-bound protein 2 (Adapter protein GRB2) (SH2/SH3 adapter GRB2)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[GAB1] GRB2-associated-binding protein 1 (GRB2-associated binder 1) (Growth factor receptor bound protein 2-associated protein 1)
[Themis] Protein THEMIS (Grb2-associating protein) (Gasp) (Protein thylex) (Thymocyte-expressed molecule involved in selection)
[MED28 EG1 FKSG20] Mediator of RNA polymerase II transcription subunit 28 (Endothelial-derived protein 1) (Mediator complex subunit 28) (Merlin and Grb2-interacting cytoskeletal protein) (Magicin) (Tumor angiogenesis marker EG-1)
[SGIP1] SH3-containing GRB2-like protein 3-interacting protein 1 (Endophilin-3-interacting protein)
[SH3GL2 CNSA2 SH3D2A] Endophilin-A1 (EEN-B1) (Endophilin-1) (SH3 domain protein 2A) (SH3 domain-containing GRB2-like protein 2)
[Sgip1] SH3-containing GRB2-like protein 3-interacting protein 1 (Endophilin-3-interacting protein)
[Sgip1] SH3-containing GRB2-like protein 3-interacting protein 1 (Endophilin-3-interacting protein)
[Sh3gl2 Sh3d2a Sh3p4] Endophilin-A1 (Endophilin-1) (SH3 domain protein 2A) (SH3 domain-containing GRB2-like protein 2) (SH3p4)
[Mapk1 Erk2 Mapk Prkm1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[MAPK1 ERK2 PRKM1 PRKM2] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[MAPK1 ERK2 PRKM1] Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2)
[Mapk3 Erk1 Prkm3] Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (MNK1) (Microtubule-associated protein 2 kinase) (p44-ERK1)
[SGIP1] SH3-containing GRB2-like protein 3-interacting protein 1 (Endophilin-3-interacting protein)
[FLT4 VEGFR3] Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4)
[FLT1 FLT FRT VEGFR1] Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase FRT) (Tyrosine-protein kinase receptor FLT) (FLT) (Vascular permeability factor receptor)
[Csf1r Csfmr Fms] Macrophage colony-stimulating factor 1 receptor (CSF-1 receptor) (CSF-1-R) (CSF-1R) (M-CSF-R) (EC 2.7.10.1) (Proto-oncogene c-Fms) (CD antigen CD115)
[Khdrbs1] KH domain-containing, RNA-binding, signal transduction-associated protein 1 (GAP-associated tyrosine phosphoprotein p62) (Src-associated in mitosis 68 kDa protein) (Sam68) (p21 Ras GTPase-activating protein-associated p62) (p68)
[PTPRJ DEP1] Receptor-type tyrosine-protein phosphatase eta (Protein-tyrosine phosphatase eta) (R-PTP-eta) (EC 3.1.3.48) (Density-enhanced phosphatase 1) (DEP-1) (HPTP eta) (Protein-tyrosine phosphatase receptor type J) (R-PTP-J) (CD antigen CD148)
[PTPN11 PTP2C SHPTP2] Tyrosine-protein phosphatase non-receptor type 11 (EC 3.1.3.48) (Protein-tyrosine phosphatase 1D) (PTP-1D) (Protein-tyrosine phosphatase 2C) (PTP-2C) (SH-PTP2) (SHP-2) (Shp2) (SH-PTP3)
[KDR FLK1 VEGFR2] Vascular endothelial growth factor receptor 2 (VEGFR-2) (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor) (KDR) (Protein-tyrosine kinase receptor flk-1) (CD antigen CD309)
[Mertk Mer] Tyrosine-protein kinase Mer (EC 2.7.10.1) (Proto-oncogene c-Mer) (Receptor tyrosine kinase MerTK)
[Flt1 Emrk2 Flt Vegfr1] Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Embryonic receptor kinase 2) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase receptor FLT)
[Flt1 Flt-1 Vegfr1] Vascular endothelial growth factor receptor 1 (VEGFR-1) (EC 2.7.10.1) (Fms-like tyrosine kinase 1) (FLT-1) (Tyrosine-protein kinase receptor FLT)

Bibliography :
[24003223] A brain-specific Grb2-associated regulator of extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) (GAREM) subtype, GAREM2, contributes to neurite outgrowth of neuroblastoma cells by regulating Erk signaling.